Rapsyn regulation of ACh receptor function

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): My main objective is to determine how rapsyn directs the increase in AChR density at the neuromuscular junction (NMJ). Severe effects on development and health result when the NMJ becomes impaired. The autoimmune disease myasthenia gravis (MG) and its genetic counterpart, congenital myasthenic syndrome (CMS), which result in muscle weakness and fatigue, are both caused by defects in specific components of the NMJ, including rapsyn in many cases. To date, analysis of rapsyn has been relegated to heterologous expression systems and ectopic NMJs in tissue culture. These studies have yet to clarify rapsyn's function and have only served to add to the controversy regarding its mode of action. Findings in wild type and mutant zebrafish stand in sharp contrast to previous research and suggest a novel mechanism for rapsyn-AChR interactions. This disparity may stem from the use of model systems that fail to authentically reconstitute neuromuscular synapses. To conclusively determined rapsyn's role in formation and maintenance of the NMJ, I will study function in true neuromuscular junctions using zebrafish as a model vertebrate system. This study may serve as a template for studies of other neuromuscular synapses.